Pharmacokinetics of sodium stibogluconate in serum at escalating doses

Clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Sodium Stibogluconate and IFNa-2b Followed By CDDP, VLB and DTIC Treating Pts.With Advanced Melanoma or Other Cancers

Official Title ICMJE

Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b Followed by Cisplatin, Vinblastine and Dacarbazine for Patients With Melanoma or Malignancies Potentially Responsive to SSG and/or Interferons

Brief Summary

RATIONALE: Sodium stibogluconate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma and other cancers. Drugs used in chemotherapy, such as cisplatin, vinblastine, and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sodium stibogluconate and interferon alfa-2b together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of sodium stibogluconate when given together with interferon alfa-2b, cisplatin, vinblastine, and dacarbazine in treating patients with advanced melanoma or other cancer.

Detailed Description

OBJECTIVES:

Primary

To determine the safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy.

To confirm the activity of sodium stibogluconate in augmenting cytokine effects.

To define the effectiveness of sodium stibogluconate in inhibiting the protein tyrosine phosphatases SHP-1 and SHP-2 assayed from peripheral blood leukocytes of patients receiving sodium stibogluconate in combination with interferon alfa-2b.

To define the pharmacokinetics of sodium stibogluconate in serum at escalating doses.

To assess clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy.

OUTLINE:

Course 1: Patients receive sodium stibogluconate IV over 15 minutes on day 1 and days 15-18; interferon alfa-2b subcutaneously (SC) on days 8-12 and 15-18; cisplatin IV over 30-60 minutes and vinblastine IV on days 19 and 20; and dacarbazine. After a 2-week rest period, patients proceed to course 2.

Course 2 and all subsequent courses: Patients receive sodium stibogluconate IV over 15 minutes and interferon alfa-2b SC on days 1-4; cisplatin IV over 30-60 minutes and vinblastine IV on days 5 and 6; dacarbazine. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.* NOTE: *Patients with stage IV disease who have no evidence of disease [NED} receive only 4 courses of therapy.

Cohorts of 6 patients receive escalating doses of sodium stibogluconate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which dose-limiting toxicity occurs (i.e., no more than 1 patient at a given dose experiences DLT).

Evaluable disease can include clinically or radiographically nonmeasurable tumor, specific tumor markers, or stage IV patients with no evidence of disease (NED)

PATIENT CHARACTERISTICS:

Inclusion criteria:

ECOG performance status 0-2

Granulocytes > 1,500/μl

Platelets > 100,000/μl

Creatinine < 1.5 x upper limit of normal (ULN)

Bilirubin < 1.5 x ULN

AST and ALT < 1.5 x ULN (unless due to hepatic metastases)

Potassium ≤ 5.0 mmol/L

Magnesium ≤ 2.4 mg/dL

Creatinine clearance ≥ 60 cc/min

Ejection fraction ≥ 50%

Exclusion criteria:

Pregnant or lactating women and fertile women or men unless surgically sterile or using effective contraception

All female patients of childbearing potential or less than 1 year postmenopausal must have a negative β-HCG pregnancy test at baseline and practice a medically acceptable method of birth control (i.e., oral contraceptives for at least 3 months, implantation of an intrauterine device for at least 2 months, or barrier methods [e.g., vaginal diaphragm, vaginal sponge, or condom with spermicidal jelly]) during and for 3 months after study initiation

History of atrial fibrillation, flutter, or other serious arrhythmia (excluding asymptomatic atrial or ventricular premature complexes) in the past 24 months

History of congestive heart failure currently requiring treatment; angina pectoris; or other severe cardiovascular disease (i.e., New York Heart Association class III or IV heart disease)